通过分子动力学探测核孔复合体通道的结构模型。
Probing a structural model of the nuclear pore complex channel through molecular dynamics.
机构信息
Beckman Institute for Advanced Science and Technology, and the Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
出版信息
Biophys J. 2010 Apr 21;98(8):1658-67. doi: 10.1016/j.bpj.2009.12.4305.
Abstract
The central pore of a nuclear pore complex (NPC) is filled with unstructured proteins that contain many FG-repeats separated by hydrophilic regions. An example of such protein is nsp1. By simulating an array of nsp1 segments, we identified, in an earlier study, a spontaneously formed brushlike structure that promises to explain selective transport in the NPC channel. Here we report four (350,000 atom, 200 ns) simulations probing this structure via its interaction with transport receptor NTF2 as well as with an inert protein. NTF2 dimers are observed to gradually enter the brush, but the inert protein is not. Both NTF2 and the inert protein are found to bind to FG-repeats, but binding periods lasted more briefly for the inert protein. A simulation also investigated the behavior of a brush made of mutant nsp1 that is known to be less effective in NPC-selective transport, finding that this brush does not attract NTF2.
摘要
核孔复合体（NPC）的中央孔充满了无结构的蛋白质，这些蛋白质含有许多由亲水区隔开的 FG 重复序列。nsp1 蛋白就是这样的一种蛋白质。通过模拟一系列 nsp1 片段，我们在之前的研究中发现了一种自发形成的刷状结构，有望解释 NPC 通道中的选择性运输。在这里，我们报告了四项（350000 个原子，200ns）模拟实验，通过其与运输受体 NTF2 以及惰性蛋白的相互作用来探测这种结构。观察到 NTF2 二聚体逐渐进入刷状结构，但惰性蛋白则不会。发现 NTF2 和惰性蛋白都与 FG 重复序列结合，但结合时间持续更短的是惰性蛋白。模拟实验还研究了已知在 NPC 选择性运输中效果较差的突变 nsp1 刷状结构的行为，发现这种刷状结构不会吸引 NTF2。
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